Radiation, adriamycin, and skin reactions: Effects of radiation and drug fractionation, hyperthermia, and tetracycline

The effect of adriamycin in combination with radiation on the skin reactions of mouse feet has been examined under a variety of experimental conditions including: (a) Hyperthermic treatment (42.8°C, 1 hr, or 42.8°C, 1/2 hr) of the foot immediately following adriamycin (10 mg/kg, ip) administration, with the former given either just before or just after X irradiation. (b) Fractionated (five daily fractions) treatments of drug and radiation in a variety of sequences over an 18-day period. In the case of the most severe hyperthermic treatment (42.8°C, 1 hr), no increased radiation reactions were observed in the presence of adriamycin. Indeed, under certain circumstances a slightly less severe reaction was observed in the adriamycin-treated animals. However, in the case of the less severe hyperthermic treatment (42.8°C, 1/2 hr) a small but significant increase in skin reactions was observed. The explanation for these observations is most probably related to the kinetics of adriamycin uptake in heated cells. In the study of fractionated drug and radiation treatments, an enhancement of reaction in those animals receiving combined modality treatment over those receiving radiation alone was seen in those groups where the initiation of drug treatment succeeded the initiation of radiation treatment by 2 to 7 days. In addition, the effect of tetracycline administered in drinking water (80 μg/ml) on the foot skin reactions in mice treated with X rays alone and in combination with hyperthermia has been studied. No significant difference in the skin reactions was seen between the tetracycline-treated animals and the controls.